Ibrutinib plus rituximab and mini-CHOP in very elderly patients with newly diagnosed DLBCL: A phase II ALLG study.

The multicenter, prospective phase II Australasian Leukaemia and Lymphoma Group (ALLG) NHL29 trial (ACTRN12615000551594) was conducted to assess the addition of ibrutinib to R-mini-CHOP (IRiC) in patients aged ≥75 years with newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL). Treatment consisted of six 21-day cycles of ibrutinib-R-mini-CHOP followed by two 21-day cycles of rituximab-ibrutinib. Co-primary endpoints were deliverability and 2-year overall survival (OS). All six cycles of R-mini-CHOP were completed in 63/79 patients (80%) with the median Average Relative Total Dose and Average Relative Dose Intensity for the entire regimen both 97% (IQR 82, 100; 88, 100). With a median follow-up of 35.5 months, the 2-year OS was 68% (95% CI, 55.6 - 77.4) with a 2-year PFS of 60.0% (95% CI, 47.7- 70.3). Median OS and PFS were 72 months (95% CI, 35 - not reached) and 40 months (95% CI, 20.4 - not reached) respectively. The overall response rate (ORR) was 76% (61/79 patients), with a complete response (CR) rate of 71% (56/79 patients). Deaths occurred in 34/79 patients (43%), including 17 from progressive disease and 5 treatment related. 67% patients experienced at least one serious adverse event. Most common adverse events were infections and diarrhea (majority grade 1-2). In both health-related quality of life measures, there was an improvement in functional and symptom scales, median health state classification score and median visual analogue scale in responders over time. In conclusion, this study showed that the addition of ibrutinib to R-mini-CHOP was both deliverable and efficacious in elderly DLBCL patients.

Healthcare resource utilization trends in patients with acute myeloid leukemia ineligible for intensive chemotherapy receiving first-line systemic treatment or best supportive care: A multicenter international study.

OBJECTIVES: This retrospective chart review examined real-world healthcare resource utilization (HRU) in patients with AML ineligible for intensive therapy who received first-line systemic therapy or best supportive care (BSC). METHODS: Data were collected anonymously on patients with AML who initiated first-line hypomethylating agents (HMA), low-dose cytarabine (LDAC), other systemic therapy, or BSC. HRU endpoints included hospitalizations, outpatient consultations, transfusions, and supportive care. RESULTS: Of 1762 patients included, 46% received HMA, 11% received LDAC, 17% received other systemic therapy, 26% received BSC; median treatment durations were 118, 35, 33, and 57 days, respectively. Most patients were hospitalized, most commonly for treatment administration, transfusion, or infection (HMA 82%, LDAC 93%, other systemic therapy 83%, BSC 83%). A median number of hospitalizations were 2-6 across systemic groups and two for BSC, with median durations of 8-18 days. Transfusion rates and outpatient consultations were highest for HMA (80% and 79%) versus LDAC (57% and 53%), other systemic therapy (57% and 63%), and BSC (71% and 66%). Antivirals/antibiotics and antifungals were used more frequently than growth factors (72-92%, 34-63%, and 7-27%, respectively). CONCLUSION: Patients with AML ineligible for intensive therapy have high HRU; novel therapies are needed to alleviate this burden.

Real-world treatment patterns and clinical outcomes in patients with AML unfit for first-line intensive chemotherapy.

Acute myeloid leukemia (AML) predominantly affects the elderly, and prognosis declines with age. Induction chemotherapy plus consolidation therapy is standard of care for fit patients; options for unfit patients include hypomethylating agents (HMA), low-dose cytarabine (LDAC), targeted therapies, and best supportive care (BSC). This retrospective chart review evaluated clinical outcomes in unfit patients with AML who initiated first-line treatment or BSC 01/01/2015-12/31/2018. Overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF), and response rates were assessed. Of 1762 patients, 1310 received systemic therapies: 809 HMA, 199 LDAC, and 302 other therapies; 452 received BSC. Median OS was 9.9, 7.9, 5.4, and 2.5 months for HMA, LDAC, other, and BSC, respectively. Median PFS was 7.5, 5.3, 4.1, and 2.1 months for HMA, LDAC, other, and BSC, respectively; median TTF was 4.9, 2.1, 2.2, and 2.1 months, respectively. Our findings highlight the unmet need for novel therapies for unfit patients.

Intensive care unit outcomes in patients with hematological malignancy.

Hematological malignancies are usually life-limiting conditions. Limitations of care need to be decided early, based on acceptability to the patient, family, physician, and community. Inappropriate intensive care unit (ICU) admission is likely to result in significant physical, psychological, and economic burden. There is little published on the impact of non-acute preadmission disease factors on ICU outcomes in hematological malignancies. Aim: To identify baseline performance and disease-associated factors before admission to ICU in patients with hematological malignancy that contribute to subsequent ICU mortality. Methods: A retrospective analysis of electronic medical records, laboratory results, and Intensive Care data for all patients (n = 184) with hematological malignancy admitted to the Calvary Mater Hospital ICU between January 1, 2013 and June 30, 2017 was undertaken. Baseline age, gender, condition, Eastern Cooperative Oncology, and Charlson Comorbidity scores were compared to ICU outcome and overall survival. Disease-specific prognostic risk scores were compared to ICU outcome. Results: Overall, 73.9% survived the ICU admission, with 31.6% surviving at 12 months. Superior ejection fractions (>55%) and prognosis >12 months (based on disease-specific risk scores) were significantly associated with overall survival (P = 0.024 and P = 0.001). Induction and posttransplantation therapy were predictive of poor ICU survival outcome (P < 0.0001 and P = 0.041). APACHE scores were significant predictors of ICU mortality (P = 0.002 for APACHE II and P < 0.0001 for APACHE III). Conclusion: Survival outcomes for patients with hematological malignancy admitted to the ICU correlate with functional and comorbidity status. Disease-specific prognostic scores can assist in recognizing patients likely to benefit from ICU admission.

Cytogenetic abnormalities in de novo acute myeloid leukemia in adults: relation to morphology, age, sex and ethnicity - a single center study from Singapore.

BACKGROUND: Cytogenetic analysis performed at diagnosis is considered to be the most valuable prognostic factor in acute myeloid leukemia (AML). Large systematic studies of cytogenetic abnormalities in AML patients from Southeast Asia are not available. The karyotypic patterns in AML patients from a single center in Singapore were studied and compared with reports from other regions of the world to identify possible geographic heterogeneity. METHODS: Analysis was performed on 501 consecutive de novo AML patients diagnosed according to the FAB criteria in the Singapore General Hospital. The cytogenetic findings were analyzed for possible associations between karyotypic pattern and the age, gender, ethnicity as well as morphological (FAB) subtypes. RESULTS: A total of 454 patients were studied of which 275(61%) had abnormal cytogenetics(median age 48 years). The t(15;17) and trisomy 8 were the most frequent karyotypic abnormalities - seen in 52(11%) and 33(7.3%) cases, respectively. Inv(lf) and t(16;16) were uncommon, seen only in five (1.1%) cases. The abnormalities del 5/5q and del 7/7q were seen in 30(6.6%) and 32(7%) of the cases. Complex karyotypes were seen in 78(17%) of the cases.Recurrent cytogenetic abnormalities correlated with the FAB subtypes. In all, 21 novel cytogenetic abnormalities were observed. CONCLUSIONS: Certain differences such as the age at presentation and frequency of recurrent balanced translocations were noted in comparison to previous reports. These point to the need for extensive epidemiological studies to clarify the role of genetic as well as geographic heterogeneity in the pathogenesis of AML.